ZAP-mediated mRNA degradation

Zhu, Young; Gao, Guangxia

doi:10.4161/rna.5.2.6044

Cited by 80 publications

(84 citation statements)

References 22 publications

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“…These activities might be differentially regulated through the ability to bind two distinct RNA helicases: RIG-I for the activation of host innate immune response and p72 RNA helicase for the degradation of viral RNAs 25,26 . How these activities are regulated remains to be clarified.…”

Section: Discussionmentioning

confidence: 99%

“…A weak increase in IFNB mRNA expression was also detected in cells expressing PARP-1, PARP-2 and PARP-9. PARP-13 exists in at least two isoforms 22,26,38 . The amino-terminal 254-amino acid fragment of the rat homologue, which corresponds to the N-terminal one-third portion of the shorter isoform of human PARP-13 protein, was previously identified as rat N-terminal zinc finger antiviral protein (rNZAP) 20 .…”

Section: Parps Contribute To the Ifn Responsementioning

confidence: 99%

“…These results suggest that ZAPS plays a crucial role in RIG-I-mediated gene induction. ZAP plays a role in the decay of mRNAs derived from certain viral subsets 20,26,39 . Our current data showing that ZAPS facilitates the activation of innate antiviral mechanisms indicates that this gene might exert a "dual-mode" defence activity against viral infection.…”

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confidence: 99%

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ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses

et al. 2010

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Japan. 8 These authors contributed equally to this work. Correspondence should be addressed to A.T. (takaoka@igm.hokudai.ac.jp). At least three DExD/H-box RNA helicases 4,5 , RIG-I, MDA5 and LGP2 are included in the RLR family. RIG-I is a key PRR for the detection of positive-and negative-stranded RNA viruses in the cytoplasm of cells 6,7 , and plays an important role in triggering responses against many viruses, such as orthomyxovirus (influenza A virus) and paramyxovirus (measles, mumps, and Sendai virus (SeV)) families, hepatitis C virus (HCV), and Japanese encephalitis virus (JEV) 8 . 5'-triphosphate modifications of RNA (3pRNA) are essential for RIG-I recognition and activation 9,10 . Ligand-binding activates the ATPase activity of RIG-I to change its structural conformation 6 , which in turn enables RIG-I to interact through its N-terminal tandem caspase recruitment domain (CARD) with the adaptor protein MAVS (for mitochondrial antiviral signaling protein, also known as IPS-1, VISA, or Cardif) [11][12][13][14] . MAVS then initiates the activation of interferon (IFN)-regulatory factor (IRF) 3, IRF7 and NF-κB transcriptional pathways for the subsequent production of type I IFNs and inflammatory cytokines, which are crucial for activating innate immune responses to viral infection 6,15 . Given the important role of the RIG-I pathway in the antiviral innate response, the mechanisms regulating RIG-I activation represent a topic of intense research [16][17][18] .Poly(ADP-ribose) polymerases (PARPs), a superfamily with least 17 members, are known to regulate not only cell survival and cell death programs triggered by DNA 3 damage, but also other biological functions as well as pathological processes, such as inflammatory and degenerative diseases, in a manner dependent or independent of their PARP activity [19][20][21][22] . Several PARP-superfamily members have a direct regulatory effect on replication of certain viruses 19,20,22,23 RESULTS 4PARPs contribute to the IFN response To investigate the role of the PARP-superfamily members in nucleic acid induced innate immune responses, we selected some of the PARP-superfamily members known to be involved in microbial infection, inflammation and immunity: PARP-1, PARP-2, PARP-7, PARP-9, 23,[31][32][33][34]. We then examined whether they have the ability to enhance the induction of IFNB mRNA in HEK293T cells in response to stimulation with three different types of nucleic acids-3pRNA, poly(rI:rC) and poly(dA-dT)•poly(dA-dT) (named poly(dA:dT) hereafter).Among the protein tested, PARP-13 uniquely showed a marked enhancing effect on IFNB mRNA expression induced by stimulation with 3pRNA, poly(rI:rC) and poly(dA:dT) ( Fig. 1a), all of which are known to activate the RIG-I-mediated pathway in HEK293T cells 9,10,[35][36][37] . A weak increase in IFNB mRNA expression was also detected in cells expressing PARP-1, PARP-2 and PARP-9. PARP-13 exists in at least two isoforms 22,26,38 . The amino-terminal 254-amino acid fragment of the rat homologue, which corresponds to the N...

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Section: Discussionmentioning

confidence: 99%

Section: Parps Contribute To the Ifn Responsementioning

confidence: 99%

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ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses

et al. 2010

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“…A last potential candidate for TE restriction is the zinc-finger anti-viral protein (ZAP), which does not belong to the TRIM family. ZAP promotes the degradation of viral mRNAs by interacting with the exosome, and may also prevent the accumulation of TE ribonucleoparticles in the cytoplasm (Zhu and Gao, 2008). Future studies should be directed toward understanding the importance of these various anti-retroviral proteins in suppressing endogenous TEs, and in particular in the germline in which TE-induced genetic modifications can irreversibly shape the host genome.…”

Section: Learning From Infectious Retrovirusesmentioning

confidence: 99%

Transposable elements in the mammalian germline: a comfortable niche or a deadly trap?

2010

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Retrotransposable elements comprise around 50% of the mammalian genome. Their activity represents a constant threat to the host and has prompted the development of adaptive control mechanisms to protect genome architecture and function. To ensure their propagation, retrotransposons have to mobilize in cells destined for the next generation. Accordingly, these elements are particularly well suited to transcriptional networks associated with pluripotent and germinal states in mammals. The relaxation of epigenetic control that occurs in the early developing germline constitutes a dangerous window in which retrotransposons can escape from host restraint and massively expand. What could be observed as risky behavior may turn out to be an insidious strategy developed by germ cells to sense retrotransposons and hold them back in check. Herein, we review recent insights that have provided a detailed picture of the defense mechanisms that concur toward retrotransposon silencing in mammalian genomes, and in particular in the germline. In this lineage, retrotransposons are hit at multiple stages of their life cycle, through transcriptional repression, RNA degradation and translational control. An organized cross-talk between PIWIinteracting small RNAs (piRNAs) and various nuclear and cytoplasmic accessories provides this potent and multilayered response to retrotransposon unleashing in early germ cells.

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“…Analysis of viral nucleic acids to determine the step at which ZAP inhibits the replication of MLV has shown that the formation of the integrated provirus is normal, but the level of viral mRNA in the cytoplasm is significantly reduced (14). Further studies have demonstrated that ZAP binds directly to viral mRNA and recruits the RNA exosome to degrade target RNA (17)(18)(19). The DEAD-box RNA helicase p72 directly interacts with ZAP as a cofactor and is required for optimal function of ZAP (20).…”

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confidence: 99%

Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation

Zhu

Chen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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337

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The zinc-finger antiviral protein (ZAP) was originally identified as a host factor that inhibits the replication of Moloney murine leukemia virus. Here we report that ZAP inhibits HIV-1 infection by promoting the degradation of specific viral mRNAs. Overexpression of ZAP rendered cells resistant to HIV-1 infection in a ZAP expression level-dependent manner, whereas depletion of endogenous ZAP enhanced HIV-1 infection. Both human and rat ZAP inhibited the propagation of replication-competent HIV-1. ZAP specifically targeted the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. We provide evidence indicating that ZAP selectively recruits cellular poly(A)-specific ribonuclease (PARN) to shorten the poly(A) tail of target viral mRNA and recruits the RNA exosome to degrade the RNA body from the 39 end. In addition, ZAP recruits cellular decapping complex through its cofactor RNA helicase p72 to initiate degradation of the target viral mRNA from the 59 end. Depletion of each of these mRNA degradation enzymes reduced ZAP's activity. Our results indicate that ZAP inhibits HIV-1 by recruiting both the 59 and 39 mRNA degradation machinery to specifically promote the degradation of multiply spliced HIV-1 mRNAs.retrovirus | host restriction factor | RNA degradation

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ZAP-mediated mRNA degradation

Cited by 80 publications

References 22 publications

ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses

ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses

Transposable elements in the mammalian germline: a comfortable niche or a deadly trap?

Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation

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